Endothelins are the most potent vasoconstrictor peptides known. Plasma endothelin (ET-1) concentrations were measured in eight migraine patients (mean age 44.5 years), two during an acute migraine attack with aura and six during an attack without aura. The mean ET-1 values were elevated in all migraine patients above the range of normal subjects, and were 10.6 (range 6.0-16.0) pg/ml in migraine patients and 3.8 (range 0.7-5.8) pg/ml in controls. We hypothesize that ET-1 may constrict cerebral vessels during the initial stage of the migraine attack.